Icosapent Ethyl’s Benefits Consistent in Patients With Prior PCI: REDUCE-IT

Much like in the overall REDUCE-IT trial, icosapent ethyl (Vascepa; Amarin) reduced a broad range of adverse clinical outcomes in the large subgroup of patients who had undergone a prior PCI, a prespecified analysis shows.

In that group, which encompassed 41.7% of the total trial population, icosapent ethyl reduced the primary composite outcome of CV death, MI, stroke, revascularization, or unstable angina by a relative 34% (25.6% vs 37.6%; HR 0.66; 95% CI 0.58-0.76) compared with placebo, with a number needed to treat (NNT) of 12, Benjamin Peterson, MD (Brigham and Women’s Hospital, Boston, MA), reported last week at TCT Connect 2020.

The prescription omega-3 fatty acid formulation—a highly purified form of eicosapentaenoic acid (EPA)—also cut the risk of a key secondary composite outcome of CV death, MI, or stroke (15.4% vs 23.5%; HR 0.66; 95% CI 0.56-0.79), with an NNT of 19.

“These data reflect the substantial impact of icosapent ethyl on the at-risk REDUCE-IT patient population, including patients with a history of prior PCI,” Peterson concluded.

REDUCE-IT included 8,179 patients with either established CVD or diabetes plus at least one other risk factor. Fasting triglyceride levels had to be at least 135 mg/dL but less than 500 mg/dL, and LDL cholesterol levels had to be greater than 40 mg/dL but no higher than 100 mg/dL on stable statin therapy. The main results showed that icosapent ethyl 4 g/day reduced the primary composite outcome and the key secondary outcome by a relative 25% and 26%, respectively.

Several analyses of the trial data have since been published. One demonstrated a 30% relative reduction in total and recurrent CV events in patients treated with icosapent ethyl. Another, which Peterson presented during the virtual Society for Cardiovascular Angiography and Interventions (SCAI) meeting earlier this year, showed a 34% relative reduction in coronary revascularization. That’s “the largest reduction in coronary revascularization reported since the early statin trials,” according to Peterson.

In the analysis presented during TCT Connect, Peterson zeroed in on the 3,408 patients (median age 63.0; 20.7% women) who had undergone PCI before the trial started. They were randomized a median of 2.9 years after their revascularization procedures.

In addition to lowering risks of the primary and secondary composite outcomes, icosapent ethyl reduced total events (RR 0.61; 95% CI 0.52-0.72) and—in prespecified hierarchical testing—a range of other outcomes, including CV death or MI; MI; urgent or emergent revascularization; CV death; hospitalization for unstable angina; stroke; and all-cause death, MI, or stroke (hazard ratios ranging from 0.59 to 0.72). All-cause death was numerically, but not significantly, lower in the icosapent ethyl group (6.2% vs 7.4%; HR 0.82; 95% CI 0.63-1.06).

The safety profile of icosapent ethyl in the PCI subgroup was similar to that seen in the overall trial, Peterson said, with treatment associated with an increase in atrial fibrillation or flutter (3.4% vs 2.2%; P = 0.04) but not bleeding (12.7% vs 12.1%; P = 0.60) or serious bleeding (3.2% vs 2.8%; P = 0.42).

Anthony Gershlick, MBBS (University of Leicester, England), who served as a discussant after Peterson’s presentation, said the translation of the overall trial results to the prior PCI subgroup, “is the most extraordinary thing I’ve seen in a long while. And please don’t take this wrong, but [it’s] almost unbelievable because if it wasn’t for the hard endpoints you’d have to say that maybe the patients were unblinded or the trial finished at the point at which they presented for their revascularization.”

We know that atheroma progression takes a long time, said Gershlick, who asked Peterson about the potential mechanism underlying the dramatic benefits observed on top of statin therapy.

Peterson said there were only modest reductions in triglycerides, so other mechanisms must be involved. In the trial, he noted, there were reductions in inflammatory markers comparable to those seen in the CANTOS trial, suggesting that there is a “strong anti-inflammatory component” as well. Moreover, the EVAPORATE trial indicated that icosapent ethyl may slow the progression of atherosclerosis, Peterson pointed out.

Pressed further on the potential plaque effects by Gershlick, Peterson said, “We all wish that there was a core lab associated with this trial to help us sort that out.”

Gershlick then asked about uptake of icosapent ethyl since the publication of the main REDUCE-IT results.

“We certainly hope to see more use of it, to be honest,” Peterson said, adding that “we hope that this can work its way into the guidelines. We hope that patients who’ve had a PCI and who are seeing us in clinic or as we’re finishing the PCI and we’re looking at them and looking at their lipid profile that we don’t stop with the LDL, that we keep looking down that lipid panel and think about the triglycerides. Because the majority of these patients may well benefit from icosapent ethyl, and this has also been confirmed in European registry data, Canadian registry data, and US registry data, where there’s quite a large subgroup of patients that will benefit from this.”